tbuckley/cabot-search huggingface dataset:
Tackling covid-19 variants
Authors: Kayoko Shioda
Journal: BMJ (2023)

Japan announced on 26 June 2023 that it may have entered its ninth wave of covid-19 infections. 1 Epidemiologists detected an increase in SARS-CoV-2 positive cases based on the national sentinel surveillance system, which includes some 5000 medical institutions across the country.The average weekly number of covid-19 cases per sentinel site increased from 1.12 in the week of 29 May to 5.11 in the week of 5 June 2023. 2XBB lineages were identified in most of the cases. 3 4Since XBB was first identified in India in August 2022, XBB lineages have spread across the world and have become the most common variant in various parts of the world.
Effectiveness of combined surgical and exercise-based interventions following primary traumatic anterior shoulder dislocation: a systematic review and meta-analysis
Authors: Vaishnavi Chiddarwar, Rutger M J de Zoete, Cameron Dickson, Timothy Lathlean
Journal: British Journal of Sports Medicine (2023)

Objective To investigate the effectiveness, risk of recurrence and return to activity (RTA) of surgery combined with exercise-based interventions (EBI) versus EBI alone after traumatic anterior shoulder dislocation (ASD). Design Systematic review and meta-analysis. Data sources Systematic literature search (MEDLINE, Web of Science, Scopus, Google Scholar). Eligibility Studies focused on EBI or EBI as a part of postoperative care for adults with an ASD, written in English, and published after 1990. We excluded diagnostic, assessment-based studies on individuals experiencing recurrent shoulder dislocations, concomitant shoulder injury, animal or cadaveric studies. Primary outcomes were dislocation RTA. Secondary outcomes were self-reported outcome measures, strength and range of motion. Random-effects meta-analysis was used to estimate the effect of EBI (SMD; Hedges’ g, RR). The Grading of Recommendations Assessment, Development and Evaluation approach was used to assess the certainty of evidence. Results Sixty studies were included (n=3598); seven were meta-analysed (n=345). The mean age of participants in the included studies was 26.71±9.19 and 56% of those included were male. Of the 60 studies included in the systematic review, 29 were fair quality (48.3%), 15 studies were good quality (25%) and 16 studies were poor quality (26.7%), (k=0.66). Individuals who underwent EBI alone were 2.03 times more likely to experience recurrent instability than individuals who underwent EBI in conjunction with surgery (RR 2.03, 95% CI 1.03 to 3.97). Individuals who underwent EBI with surgery appeared 1.81 times more likely to RTA than those who underwent EBI alone, although results were not statistically significant (RR 1.81, 95% CI 0.96 to 3.43). Conclusions Surgery combined with EBI is more effective in reducing the risk of recurrence and possibly increasing RTA than EBI alone after traumatic ASD.
Discovery of a glutathione utilization pathway in Francisella that shows functional divergence between environmental and pathogenic species
Authors: Yaxi Wang, Hannah E. Ledvina, Catherine A. Tower, Stanimir Kambarev, Elizabeth Liu, James C. Charity, Lieselotte S.M. Kreuk, Qing Tang, Qiwen Chen, Larry A. Gallagher, Matthew C. Radey, Guilhem F. Rerolle, Yaqiao Li, Kelsi M. Penewit, Serdar Turkarslan, Shawn J. Skerrett, Stephen J. Salipante, Nitin S. Baliga, Joshua J. Woodward, Simon L. Dove, S. Brook Peterson, Jean Celli, Joseph D. Mougous
Journal: Cell Host & Microbe (2023)

Glutathione (GSH) is an abundant metabolite within eukaryotic cells that can act as a signal, a nutrient source, or serve in a redox capacity for intracellular bacterial pathogens. For Francisella, GSH is thought to be a critical in vivo source of cysteine; however, the cellular pathways permitting GSH utilization by Francisella differ between strains and have remained poorly understood. Using genetic screening, we discovered a unique pathway for GSH utilization in Francisella. Whereas prior work suggested GSH catabolism initiates in the periplasm, the pathway we define consists of a major facilitator superfamily (MFS) member that transports intact GSH and a previously unrecognized bacterial cytoplasmic enzyme that catalyzes the first step of GSH degradation. Interestingly, we find that the transporter gene for this pathway is pseudogenized in pathogenic Francisella, explaining phenotypic discrepancies in GSH utilization among Francisella spp. and revealing a critical role for GSH in the environmental niche of these bacteria.
Real-life comparison of mortality in patients with SARS-CoV-2 infection at risk for clinical progression treated with molnupiravir or nirmatrelvir plus ritonavir during the Omicron era in Italy: a nationwide, cohort study
Authors: Carlo Torti, Pier Paolo Olimpieri, Paolo Bonfanti, Carlo Tascini, Simone Celant, Danilo Tacconi, Emanuele Nicastri, Evelina Tacconelli, Bruno Cacopardo, Alessandro Perrella, Giovanni Battista Buccoliero, Giustino Parruti, Matteo Bassetti, Carlo Biagetti, Andrea Giacometti, Elke Maria Erne, Maria Frontuto, Massimiliano Lanzafame, Valentina Summa, Alessandra Spagnoli, Annarita Vestri, Giovanni Di Perri, Pierluigi Russo, Giorgio Palù
Journal: The Lancet Regional Health - Europe (2023)

Comparative data on mortality in COVID-19 patients treated with molnupiravir or with nirmatrelvir plus ritonavir are inconclusive. We therefore compared all-cause mortality in community-dwelling COVID-19 patients treated with these drugs during the Omicron era.
The Efficacy and Safety of Prasugrel With and Without a Glycoprotein IIb/IIIa Inhibitor in Patients With Acute Coronary Syndromes Undergoing Percutaneous Intervention
Authors: Michelle O'Donoghue, Elliott M. Antman, Eugene Braunwald, Sabina A. Murphy, P. Gabriel Steg, Ariel Finkelstein, William F. Penny, Viliam Fridrich, Carolyn H. McCabe, Marc S. Sabatine, Stephen D. Wiviott
Journal: Journal of the American College of Cardiology (2009)
Hypoxic niches attract and sequester tumor-associated macrophages and cytotoxic T cells and reprogram them for immunosuppression
Authors: Anirudh Sattiraju, Sangjo Kang, Bruno Giotti, Zhihong Chen, Valerie J. Marallano, Concetta Brusco, Aarthi Ramakrishnan, Li Shen, Alexander M. Tsankov, Dolores Hambardzumyan, Roland H. Friedel, Hongyan Zou
Journal: Immunity (2023)
A Natural Self‐Assembled Gel‐Sponge with Hierarchical Porous Structure for Rapid Hemostasis and Antibacterial
Authors: Na Li, Guoqin Zhang, Yi Liu, Lili Sun, Xin Zhao, Liqin Ding, Yanan Liu, Meng Wang, Xiaoliang Ren
Journal: Advanced Healthcare Materials (2023)

Developing hemostatic agents with reliable biosafety and high efficiency has paramount clinical significance for saving lives. Herein, inspired from traditional Chinese medicine, a sponge (BC-S) with hierarchical porous structure is proposed for the treatment of bleeding. The BC-S is prepared by a simple self-assembly method employing Bletilla Striata polysaccharide and quaternary amine alkaloids (QA) from Bletilla Striata and Coptidis Rhizoma. The ideal cation donor encapsulated in the helical structure of BSP enlarges the inter-layer space of sponge by the action of electrostatic repulsion, forming wider channels which can accelerate the diversion speed of absorbed blood. Then, platelets and erythrocytes are trapped tightly in the reticular structure and extruded to deformation, activation. Subsequently, fibrin network forms and reinforces the internal multilayer mesh, blocks the outflow of blood. QA is released from the sponge skeleton mainly driven by a combination of surface erosion and potentially solution diffusion among pore to provide long-term antibacterial activity. Benefiting from the well-designed structure and the effective hemostatic mechanism, the BC-S displays more excellent hemostatic performance in different models in vivo and in vitro compared with typical gelatin hemostatic sponge. This work is expected to boost the development of emerging hemostatic agents.
Shackling incarcerated people in Israeli hospitals—a multicentre study followed by a national intervention programme
Authors: Nitai Bar, Efrat Naaman, Danny Rosin, Eliad Aviram, Henit Yanai, Noam Yehudai, Raphael Walden, Hagit Padova, Michal Kori, Maya Peled-Raz, Dalya Tedgi, Eyad Kabha, Baruch Yerushalmi, Ziv Gil, Nurit Wagner, Tamar Karni, Dan Turner
Journal: The Lancet (2023)
Artificial Intelligence for Drug Discovery: Are We There Yet?
Authors: Catrin Hasselgren, Tudor I. Oprea
Journal: The Annual Review of Pharmacology and Toxicology (2023)

Drug discovery is adapting to novel technologies such as data science, informatics, and artificial intelligence (AI) to accelerate effective treatment development while reducing costs and animal experiments. AI is transforming drug discovery, as indicated by increasing interest from investors, industrial and academic scientists, and legislators. Successful drug discovery requires optimizing properties related to pharmacodynamics, pharmacokinetics, and clinical outcomes. This review discusses the use of AI in the three pillars of drug discovery: diseases, targets, and therapeutic modalities, with a focus on small molecule drugs. AI technologies, such as generative chemistry, machine learning, and multi-property optimization, have enabled several compounds to enter clinical trials. The scientific community must carefully vet known information to address the reproducibility crisis. The full potential of AI in drug discovery can only be realized with sufficient ground truth and appropriate human intervention at later pipeline stages.
Dual mRNA co-delivery for in situ generation of phagocytosis-enhanced CAR macrophages augments hepatocellular carcinoma immunotherapy
Authors: Zhenmei Yang, Ying Liu, Kun Zhao, Weiqiang Jing, Lin Gao, Xianghui Dong, Yan Wang, Maosen Han, Chongdeng Shi, Chunwei Tang, Peng Sun, Rui Zhang, Zhipeng Fu, Jing Zhang, Danqing Zhu, Chen Chen, Xinyi Jiang
Journal: Journal of Controlled Release (2023)
Biofunctionalization of 3D printed collagen with bevacizumab-loaded microparticles targeting pathological angiogenesis
Authors: Anna Abbadessa, Paulina Nuñez Bernal, Giorgio Buttitta, Alfredo Ronca, Ugo D'Amora, Carla Zihlmann, Niklaus Stiefel, Luigi Ambrosio, Jos Malda, Riccardo Levato, José Crecente-Campo, María José Alonso
Journal: Journal of Controlled Release (2023)

Pathological angiogenesis is a crucial attribute of several chronic diseases such as cancer, age-related macular degeneration, and osteoarthritis (OA). In the case of OA, pathological angiogenesis mediated by the vascular endothelial growth factor (VEGF), among other factors, contributes to cartilage degeneration and to implants rejection. In line with this, the use of the anti-VEGF bevacizumab (BVZ) has been shown to prevent OA progression and support cartilage regeneration. The aim of this work was to functionalize a medical grade collagen with poly (lactic-co-glycolic acid) (PLGA) microparticles containing BVZ via three-dimensional (3D) printing to target pathological angiogenesis. First, the effect of several formulation parameters on the encapsulation and release of BVZ from PLGA microparticles was studied. Then, the anti-angiogenic activity of released BVZ was tested in a 3D cell model. The 3D printability of the microparticle-loaded collagen ink was tested by evaluating the shape fidelity of 3D printed structures. Results showed that the release and the encapsulation efficiency of BVZ could be tuned as a function of several formulation parameters. In addition, the released BVZ was observed to reduce vascularization by human umbilical vein endothelial cells. Finally, the collagen ink with embedded BVZ microparticles was successfully printed, leading to shape-stable meniscus-, nose- and auricle-like structures. Taken altogether, we defined the conditions for the successful combination of BVZ-loaded microparticles with the 3D printing of a medical grade collagen to target pathological angiogenesis.
The allopurinol metabolite, oxypurinol, drives oligoclonal expansions of drug‐reactive T cells in resolved hypersensitivity cases and drug‐naïve healthy donors
Authors: Nicole A. Mifsud, Patricia T. Illing, Rebecca Ho, Johanna E. Tuomisto, Heidi Fettke, Kerry A. Mullan, James McCluskey, Jamie Rossjohn, Julian Vivian, Rangsima Reantragoon, Anthony W. Purcell
Journal: Allergy (2023)

Abstract Allopurinol (ALP) is a successful drug used in the treatment of gout. However, this drug has been implicated in hypersensitivity reactions that can cause severe to life‐threatening reactions such as Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Individuals who carry the human leukocyte antigen (HLA)‐B*58:01 allotype are at higher risk of experiencing a hypersensitivity reaction (odds ratios ranging from 5.62 to 580.3 for mild to severe reactions, respectively). In addition to the parent drug, the metabolite oxypurinol (OXP) is implicated in triggering T cell‐mediated immunopathology via a labile interaction with HLA‐B*58:01. To date, there has been limited information regarding the T‐cell receptor (TCR) repertoire usage of reactive T cells in patients with ALP‐induced SJS or TEN and, in particular, there are no reports examining paired αβTCRs. Here, using in vitro drug‐treated PBMCs isolated from both resolved ALP‐induced SJS/TEN cases and drug‐naïve healthy donors, we show that OXP is the driver of CD8 + T cell‐mediated responses and that drug‐exposed memory T cells can exhibit a proinflammatory immunophenotype similar to T cells described during active disease. Furthermore, this response supported the pharmacological interaction with immune receptors (p‐i) concept by showcasing (i) the labile metabolite interaction with peptide/HLA complexes, (ii) immunogenic complex formation at the cell surface, and (iii) lack of requirement for antigen processing to elicit drug‐induced T cell responsiveness. Examination of paired OXP‐induced αβTCR repertoires highlighted an oligoclonal and private clonotypic profile in both resolved ALP‐induced SJS/TEN cases and drug‐naïve healthy donors.
Hydrogel device for analgesic drugs with in-situ loading and polymerization
Authors: Scott Grindy, Dmitry Gil, Jeremy Suhardi, Yingfang Fan, Kyle Moore, Shannon Hugard, Charlotte Leape, Mark Randolph, Mehmet D. Asik, Orhun Muratoglu, Ebru Oral
Journal: Journal of Controlled Release (2023)
Cabazitaxel prodrug nanoassemblies with branched chain modifications: Narrowing the gap between efficacy and safety
Authors: Hezhen Xu, Shiyi Zuo, Danping Wang, Yu Zhang, Wenxiao Li, Lingxiao Li, Tian Liu, Yuanhao Yu, Qingzhi Lv, Zhonggui He, Jin Sun, Bingjun Sun
Journal: Journal of Controlled Release (2023)
Clinical periodontal diagnosis
Authors: Giovanni E. Salvi, Andrea Roccuzzo, Jean‐Claude Imber, Alexandra Stähli, Björn Klinge, Niklaus P. Lang
Journal: Periodontology 2000 (2023)

Abstract Periodontal diseases include pathological conditions elicited by the presence of bacterial biofilms leading to a host response. In the diagnostic process, clinical signs such as bleeding on probing, development of periodontal pockets and gingival recessions, furcation involvement and presence of radiographic bone loss should be assessed prior to periodontal therapy, following active therapy, and during long‐term supportive care. In addition, patient‐reported outcomes such as increased tooth mobility, migration, and tilting should also be considered. More important to the patient, however, is the fact that assessment of signs of periodontal diseases must be followed by an appropriate treatment plan. Furthermore, it should be realized that clinical and radiographic periodontal diagnosis is based on signs which may not reflect the presence of active disease but rather represent the sequelae of a previous bacterial challenge. Hence, the aim of the present review is to provide a summary of clinical and radiographic diagnostic criteria required to classify patients with periodontal health or disease.
Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions: reevaluation of the defining characteristics in a registry-based cohort
Authors: Georgia Metzgeroth, Laurenz Steiner, Nicole Naumann, Johannes Lübke, Sebastian Kreil, Alice Fabarius, Claudia Haferlach, Torsten Haferlach, Wolf-Karsten Hofmann, Nicholas C. P. Cross, Juliana Schwaab, Andreas Reiter
Journal: Leukemia (2023)

In a registry-based analysis of 135 patients with "myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions" (MLN-TK; FIP1L1::PDGFRA, n = 78; PDGFRB, diverse fusions, n = 26; FGFR1, diverse, n = 9; JAK2, diverse, n = 11; ETV6::ABL1, n = 11), we sought to evaluate the disease-defining characteristics. In 81/135 (60%) evaluable patients, hypereosinophilia (>1.5 × 109/l) was observed in 40/44 (91%) FIP1L1::PDGFRA and 7/7 (100%) ETV6::ABL1 positive patients but only in 13/30 (43%) patients with PDGFRB, FGFR1, and JAK2 fusion genes while 9/30 (30%) patients had no eosinophilia. Monocytosis >1 × 109/l was identified in 27/81 (33%) patients, most frequently in association with hypereosinophilia (23/27, 85%). Overall, a blast phase (BP) was diagnosed in 38/135 (28%) patients (myeloid, 61%; lymphoid, 39%), which was at extramedullary sites in 18 (47%) patients. The comparison between patients with PDGFRA/PDGFRB vs. FGFR1, JAK2, and ETV6::ABL1 fusion genes revealed a similar occurrence of primary BP (17/104, 16% vs. 8/31 26%, p = 0.32), a lower frequency (5/87, 6% vs. 8/23, 35%, p = 0.003) of and a later progression (median 87 vs. 19 months, p = 0.053) into secondary BP, and a better overall survival from diagnosis of BP (17.1 vs. 1.7 years, p < 0.0008). We conclude that hypereosinophilia with or without monocytosis and various phenotypes of BP occur at variable frequencies in MLN-TK.
Do Nonprofit Hospitals Deserve Their Tax Exemption?
Authors: Ge Bai, Sunjay Letchuman, David A. Hyman
Journal: New England Journal of Medicine (2023)

Interview with Ge Bai on whether nonprofit hospitals provide enough community benefit to justify favored tax status. (09:02)Download Data suggest that many nonprofit hospitals don't provide enough charity care or have a substantial enough Medicaid shortfall (relative to for-profit hospitals) to justify their favorable tax treatment.
Toward a Stronger Post-Pandemic Nursing Workforce
Authors: Peter Buerhaus, Erin Fraher, Bianca Frogner, Melinda Buntin, Monica O’Reilly-Jacob, Sean Clarke
Journal: New England Journal of Medicine (2023)

The deep effects of the Covid-19 pandemic on frontline health care providers have given rise to concerns about the demands of nursing work and the appeal of nursing careers. How can we turn the tide?
The ‘pet effect’ and trans people: Associations between living with animal companions and wellbeing, social support, and trans-related marginalization in three international studies
Authors: Georgia E. Grey, Gareth J. Treharne, Damien W. Riggs, Kimberly A. Fuller, Nik Taylor, Heather Fraser
Journal: International Journal of Transgender Health (2023)

The love, joy and sense of connection between humans and animal companions can bring shared health benefits. Often this is referred to as the 'pet effect'. Previous research on the 'pet effect' suggests that living with an animal companion, and especially one who is considered part of the family, can increase human wellbeing, though to date research has rarely focused on trans people and the 'pet effect'.
Understanding the context of positive experiences of primary care for transgender and gender diverse adults: An email interview study in Aotearoa New Zealand
Authors: Cassie Withey-Rila, Kate C. Morgaine, Gareth J. Treharne
Journal: International Journal of Transgender Health (2023)

Past research has demonstrated that transgender and gender diverse (TGD) people often have negative experiences of healthcare. Exploratory research is needed to provide in-depth understanding of the healthcare experiences of TGD people. Primary care is a crucial element of healthcare, but past research has tended to overlook what contributes specifically to positive experiences of primary care for TGD adults.
Novel aspect of neprilysin in kidney fibrosis via ACSL4‐mediated ferroptosis of tubular epithelial cells
Authors: Weijing Lai, Rongshuang Huang, Bo Wang, Min Shi, Fan Guo, Lingzhi Li, Qian Ren, Sibei Tao, Ping Fu, Liang Ma
Journal: MedComm (2023)

Abstract Although inhibition of neprilysin (NEP) might be a therapeutic strategy with the potential to improve the outcome of chronic kidney disease (CKD), the versatile function of NEP with its mechanism remains obscure in kidney fibrosis. In the study, we found that NEP was abnormally increased in tubular epithelial cells of CKD patients, as well as unilateral ureteral obstruction and adenine diet‐induced mice. Treatment with a United States Food and Drug Administration‐approved NEP inhibitor Sacubitrilat (LBQ657) could alleviate ferroptosis, tubular injury, and delay the progression of kidney fibrosis in experimental mice. Similarly, genetic knockdown of NEP also inhibited tubular injury and fibrosis in transforming growth factor (TGF)‐β1 ‐induced tubular cells. Mechanically, NEP overexpression aggravated the ferroptotic and fibrotic phenotype, which was restored by acyl‐CoA synthetase long‐chain family member 4 (ACSL4) knockdown. The NEP silencing attenuated TGF‐β1‐induced tubular cell ferroptosis and was exacerbated by ACSL4 overexpression. Collectively, for the first time, a novel aspect of NEP was explored in kidney fibrosis through ACSL4‐mediated tubular epithelial cell ferroptosis. Our data further confirmed that NEP inhibition exerted a promising therapeutic against fibrotic kidney diseases.
Nanoparticles‐induced potential toxicity on human health: Applications, toxicity mechanisms, and evaluation models
Authors: Lihui Xuan, Zhao Ju, Magdalena Skonieczna, Ping‐Kun Zhou, Ruixue Huang
Journal: MedComm (2023)

Nanoparticles (NPs) have become one of the most popular objects of scientific study during the past decades. However, despite wealth of study reports, still there is a gap, particularly in health toxicology studies, underlying mechanisms, and related evaluation models to deeply understanding the NPs risk effects. In this review, we first present a comprehensive landscape of the applications of NPs on health, especially addressing the role of NPs in medical diagnosis, therapy. Then, the toxicity of NPs on health systems is introduced. We describe in detail the effects of NPs on various systems, including respiratory, nervous, endocrine, immune, and reproductive systems, and the carcinogenicity of NPs. Furthermore, we unravels the underlying mechanisms of NPs including ROS accumulation, mitochondrial damage, inflammatory reaction, apoptosis, DNA damage, cell cycle, and epigenetic regulation. In addition, the classical study models such as cell lines and mice and the emerging models such as 3D organoids used for evaluating the toxicity or scientific study are both introduced. Overall, this review presents a critical summary and evaluation of the state of understanding of NPs, giving readers more better understanding of the NPs toxicology to remedy key gaps in knowledge and techniques.
Immunotherapy: an emerging modality to checkmate brain metastasis
Authors: Aatiya Ahmad, Parvez Khan, Asad Ur Rehman, Surinder Kumar Batra, Mohd Wasim Nasser
Journal: Molecular Cancer (2023)

Abstract The diagnosis of brain metastasis (BrM) has historically been a dooming diagnosis that is nothing less than a death sentence, with few treatment options for palliation or prolonging life. Among the few treatment options available, brain radiotherapy (RT) and surgical resection have been the backbone of therapy. Within the past couple of years, immunotherapy (IT), alone and in combination with traditional treatments, has emerged as a reckoning force to combat the spread of BrM and shrink tumor burden. This review compiles recent reports describing the potential role of IT in the treatment of BrM in various cancers. It also examines the impact of the tumor microenvironment of BrM on regulating the spread of cancer and the role IT can play in mitigating that spread. Lastly, this review also focuses on the future of IT and new clinical trials pushing the boundaries of IT in BrM.